Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo

Abstract

BackgroundLevosimendan and its long-lived metabolite OR-1896 produce vasodilation in different types of vessels by activating ATP-sensitive (KATP) and other potassium channels. MethodsIn the present study we applied intravital videomicroscopy to investigate the in situ effects of levosimendan and OR-1896 on the diameters of real resistance arterioles (rat cremaster muscle arterioles with diameters of ~ 20μm). ResultsLevosimendan and OR-1896 induced concentration-dependent (1nM – 100μM) dilations to similar extents in these arterioles (maximal dilation from 23±2 to 33±2μm and from 22±1 to 32±1μm, respectively). The arteriolar dilations induced by the selective KATP channel opener pinacidil (1nM – 10μM) (maximal dilation from 22±4μm to 35±3μm) were diminished in the presence of the selective KATP channel blocker – glibenclamide (5μM) (maximal diameter attained: 22±1μm). Glibenclamide also counteracted the maximal dilations in response to levosimendan or OR-1896 (to 23±3μm or 22±5μm, respectively). ConclusionsIn conclusion, this is the first demonstration that levosimendan and OR-1896 elicit arteriolar dilation in vivo, via activation of KATP channels in real resistance vessels in the rat.